Phosphatidylinositol 3'-kinase is associated with a serine kinase that is activated by okadaic acid.
Okadaic acid (OA) is a potent inhibitor of PP1 and PP2A serine/threonine phosphatases and an inhibitor of phosphatidylinositol 3'-kinase (PI 3-kinase) recruitment/ activation. Here we report that PI 3-kinase associates with a serine kinase activated by OA. Whole cell phosphorylation studies showed that PI 3-kinase associates with a wortmannin insensitive 76 kDa serine phosphoprotein (pp76) distinct from the p85 subunit of PI 3-kinase. Serine kinase assays demonstrated that pp76 phosphorylation was dependent upon a wortmannin insensitive serine kinase contained within PI 3-kinase/pp76 complexes and that this kinase had different cation requirements than PI 3-kinase serine kinase. Treatment of whole cells with OA lead to a wortmannin-independent 7.6-fold increase in pp76 serine phosphorylation and to a 7-fold rise in pp76 kinase activity. Together, these findings indicate that pp76 is a PI 3-kinase associated phosphoprotein and suggest that pp76 may be a novel PI 3-kinase associated serine kinase that is activated by OA.
Cengel
K A
KA
Department of Pathology, University of Illinois at Urbana-Champaign 61801, USA.
Godbout
J P
JP
Freund
G G
GG
D000730:Androstadienes / Q000494:pharmacology; D015153:Blotting, Western; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009101:Multiple Myeloma; D019319:Okadaic Acid / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D019319:Okadaic Acid; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; D000077191:Wortmannin